The project aim is to determine at the molecular level the mechanism of an inhibition of protein synthesis initiation which is activated in human and other mammalian cells by conditions which decrease the charging of tRNA with amino acids. We have recently determined that this regulation is mediated at, or prior to, the synthesis of the 40S-Met-tRNAi initiation complex. Our immediate goal in the next year is to determine whether the mechanism of the regulation depends on phosphorylation of initation factor eIF-2. If this is the case we will seek to identify the kinase involved and determine how its activation is related to the state of charging of tRNA.